Alkylidenation esters

F.N. Tebbe (1978 [footnote 20]) and R.R. Schrock (1976) have shown that electrophilic titanium or tantalum ylides can alkylidenate the carbonyl group of esters. Vinyl ethers are obtained in high yields with Tebbe s reagent, p-chlorobis(ri -2,4-cyclopentadien-l-ylXdime-thylaluminum)- 4-methylenetitanium (S.H. Pine, 1980 A.G.M. Barrett, 1989). 

The 2,3-alkadienyl esters 839 are reactive compounds toward Pd catalysts and form the a-alkylidene-rr-allylpalladium complexes 840, which react further to give two kinds of products, namely the 1,2- and 1,4-diene derivatives 841 and 842, depending on the reactants. 

Table 23. Preparation of Ethyl Alkylidene Fluoroacetates RCH=CFCOOEt from Esters Reduced in situ with Diisobuty laluminum Hydride [73]...

Optically active substituted alkylidene cyclohexanes were prepared from sulfinyl esters (obtained by carboxylation of sulfinyl anions) by thermolytic elimination of the sulfinyl group65. 

Oxo esters are accessible via the diastereoselective 1,4-addition of chiral lithium enamine 11 as Michael donor. The terr-butyl ester of L-valine reacts with a / -oxo ester to form a chiral enamine which on deprotonation with lithium diisopropylamide results in the highly chelated enolate 11. Subsequent 1,4-addition to 2-(arylmethylene) or 2-alkylidene-l,3-propanedioates at — 78 °C, followed by removal of the auxiliary by hydrolysis and decarboxylation of the Michael adducts, affords optically active -substituted <5-oxo esters232 (for a related synthesis of 1,5-diesters, see Section 1.5.2.4.2.2.1.). In the same manner, <5-oxo esters with contiguous quaternary and tertiary carbon centers with virtually complete induced (> 99%) and excellent simple diastereoselectivities (d.r. 93 7 to 99.5 0.5) may be obtained 233 234. 

Further work by the Ye group has shown that NHCs derived from pre-catalyst 215 can also promote the asymmetric dimerisation of alkylarylketenes 193 to generate alkylidene P-lactones 216 in good diastereo- and enantio-selectivity [83], The asymmetric [4+2] addition of enones and alkylarylketenes to generate 8-lactones 218 in high ee has also been accomplished [84], as has the asymmetric esterification of alkylarylketenes to give esters 217 using benzhydrol, which is assumed to proceed via a Lewis-base mediated mechanism (Scheme 12.46) [85]. 

A unique approach to the requisite C-ring fragment 51 is achieved through reductive cyclization of olefinic ester 55 by way of the titanium alkylidene, as described by Rainer and Nicolaou [59]. The olefinic ester 55 is prepared in ten steps from (R)-isobutyl lactate using consecutive chelation-controlled... 

Some interesting fused 1,2,3-triazole ring systems have been reported. A series of 5-piperidyl-substituted 7-hydroxy-3f/-l,2,3-triazolo[4,5-d]pyrimidines 143 has been synthesized from pipecolinate esters, benzylazides, and cyanoacetamide <06CHE246>. 4-Alkylidene-5,6-dihydro-4//-pyrrolo-[l,2-c][l,2,3]triazoles 144 were prepared from alkylidenecyclopropanes via diiodogenation/Cu(I)-catalyzed 1,3-dipolar cycloaddition/intra-molecular Heck reaction sequence <06SL1446>. 6,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydro-27/-benzotriazol-4-one 145 were prepared from A-(5,5-dimethyl-3-oxocyclohexenyl)-S,S-diphenylsulfilimine and... 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

Recently, Nicolaou and coworkers have devised a novel, one-pot strategy for the direct transformation of acyclic olefinic esters to cyclic enol ethers [34]. Unlike the molybdenum alkylidene 1 (see Sect. 3.2), initial reaction between the Tebbe reagent 93 and an olefinic ester results in rapid carbonyl olefination to afford a diene intermediate. Subsequent heating initiates RCM to afford the desired cyclic product (Scheme 17). 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

Alkylidenation of silyl esters.1 Application of this alkylidenation process to silyl esters provides (Z-)silyl enol ethers stereoselectively. 

Carbonylation of 4-en-2-ynyl carbonates offers a novel synthetic method for cross-conjugated 4-oxo-5-alkylidene-2-cyclopentenecarboxylates (Scheme 16.35) [38]. The primary product of the process appears to be a 2-vinyl-2,3-dienyl ester, leading to a palladacycle, which in turn follows CO insertion into the Pd-sp2 carbon, reductive elimination of Pd(0) species and isomerization, leading to the final product. 

The synthesis of the pyridine ring from ethyl acetoacetate, aldehydes, and ammonia proceeds extraordinarily readily. The mechanism is as follows. In the first phase the aldehydes react with the acetoacetic ester to form alkylidene bis-acetoacetic esters. The 1 5-diketone derivatives so formed undergo ring closure by introduction of a molecule of ammonia and elimination of two molecules of water ... 

Alkylidene cyclohexenes were synthesized stereoselectively from bis-allyl silylketene acetals derived from cyclohexenones93. As shown in equation 66, Ireland Claisen rearrangement of ester 133 gave only E-diene 136. Reaction of 133 with potassium... 

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